A Dose-finding Trial of Hyperthermic Intraperitoneal Docetaxel

Phase 1

• Conditions: Hyperthermic Intraperitoneal Chemotherapy
• Interventions: Drug: Docetaxel

• Registration Number: NCT05410483
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

This is a single-center study design, and 30 patients will be enrolled. Eligible patients will receive docetaxel at different dose levels according to the trial schedule.All the enrolled patients were treated with docetaxel during the first HIPEC treatment and cisplatin during the second HIPEC treatment at 43℃ for 1 hour.The dose of docetaxel for patients in the next group was determined according to the incidence of dose-limiting toxicity (DLT) of the previous docetaxel dose level. Finally, the maximum tolerated dose (MTD) of docetaxel for HIPEC was calculated according to the incidence of dose-limiting toxicity.

Detailed Description

This is a single-center study design, and 30 patients will be enrolled. Eligible patients will receive docetaxel at different dose levels according to the trial schedule. All the enrolled patients were treated with docetaxel during the first HIPEC treatment and cisplatin during the second HIPEC treatment at 43℃ for 1 hour. Four dosages of docetaxel were set up in the study. We decided to take the initial dose of 60mg/m2 and increase the remaining dose gradient by 5 mg/m2. The dosage of cisplatin was 75mg/m2. Time-to-event Bayesian Optimal Interval Design(TITE-BOIN) was used, with 3 patients as an observation group (i.e. a cohort), starting from a dose of 60mg/m2. The dose of docetaxel for patients in the next group was determined according to the incidence of dose-limiting toxicity (DLT) of the previous docetaxel dose level. Finally, the maximum tolerated dose (MTD) of docetaxel for HIPEC was calculated according to the incidence of dose-limiting toxicity.

Study Timeline

• Study Start: 2022-03-01
• Status Verified: 2022-05
• Study First Submitted: 2022-05-31
• Study First Submitted QC: 2022-06-06
• Last Update Submitted: 2022-06-06
• Study First Posted: 2022-06-08
• Last Update Posted: 2022-06-08
• Primary Completion: 2023-02-01
• Study Completion: 2023-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. According to the gynecology malignant tumor abdominal hot perfusion chemotherapy clinical expert consensus, with HIPEC treatment indications, including the initial treatment of ovarian cancer, recurrent ovarian cancer, peritoneum pseudo myxoma, accompanied by abdominal cavity effusion or disseminated other gynecological malignant tumors of peritoneal cavity transfer, branch caused by malignant tumors refractory peritoneal effusion, Uterine sarcoma found after the use of tumor (uterine) device, ovarian mucous tumor before or during the rupture, a large amount of mucus overflow contamination of the abdominal cavity.
2. Ages 18 to 70.
3. Serum creatinine was within the normal range (reference range of creatinine: 58-96μmol/L) before receiving HIPEC, and renal function was normal.
4. No bone marrow suppression before HIPEC (considering many factors affecting hemoglobin level, including intraoperative blood loss and postoperative fluid infusion hemodilution, hemoglobin ≥80g/L was set; Leukocyte ≥ 4.0*109/L, granulocyte ≥ 2.0×109/L; Platelet ≥ 100×109/L).
5. No abnormal liver function before receiving HIPEC (total bilirubin 3.4-22.2μmol/L, ALT 7-40 U/L, AST 13-35U/L, AST/ALT≤1.5).
6. Signed informed consent and received docetaxel and cisplatin HIPEC treatment.

Exclusion Criteria

1. Contraindications to HIPEC: intestinal obstruction; Extensive adhesion in peritoneal cavity; The abdominal cavity has obvious inflammation; There may be high risk factors for poor postoperative anastomotic healing, including anastomotic tissue edema, ischemia, obvious tension, severe hypoproteinemia, etc. Dysfunction of major organs such as heart, kidneys, liver and brain; Severe coagulopathy; Bile obstruction and ureteral obstruction.
2. No history of radiotherapy or chemotherapy in recent 3 weeks.
3. In addition to HIPEC, docetaxel and cisplatin should be used by other means within 3 weeks after HIPEC treatment.
4. Those who have taken drugs that damage liver and kidney function or inhibit bone marrow within 3 months.
5. Allergic to docetaxel and cisplatin.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Docetaxel dose level	Docetaxel	Initial dose of 60mg/m2 and increase the remaining dose gradient by 5 mg/m2

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of docetaxel	21 days	The MTD of docetaxel for abdominal thermal perfusion was calculated by observing the incidence of dose-limiting toxicity 3 weeks after the end of HIPEC.

Secondary Outcome Measures

Name	Time	Method
Effect of dose on tumor control rate	9 weeks	The decrease of serum CA125 and HE4 concentrations and the results of imaging evaluation at different doses of docetaxel
Incidence of DLT	9 weeks	Number of DLT cases at current dose/total cases at current dose

Trial Locations

Locations (1)

Sun Yat-sen Memorial Hospital; 🇨🇳 Guangzhou, Other (Non U.s.), China